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November 28, 2012--------News Archive Return to: News Alerts

Whether these shortened DNA nibs (telomeres) at the end of our chromosomes are
harbingers of death or actually contribute to our downfall remains in question.

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Massive Genomics Project Answers Questions, Poses New Ones In Health, Genetics and Aging

Initial research findings focus on telomere trends within ethnicity, socioeconomic status, and lifestyle revealing that people with the shortest telomeres really do have a date with the Grim Reaper – according to the largest and most diverse genomics, health and longevity project in the nation

Among the initial results from the
Grand Opportunity Project on genetics,
health, aging and the environment
– a joint project between Kaiser Permanente and UCSF –
is the finding that the 10 percent of people with the
shortest telomere lengths had more than a 20 percent
higher risk of dying during the ensuing three years
than any other group.

But whether these shortened DNA nibs at the end of our chromosomes are harbingers of death or actually contribute to our downfall remains in question.

The new findings, and the increasing questions they pose, are some of the first results to emerge from the Kaiser Permanente-UCSF project that was launched in 2009 as the scientific equivalent of the large-scale infrastructure projects of the 1930s, such as the Golden Gate Bridge and the Hoover Dam.

Joining Forces for Massive Genetic Analysis

Supported with $25 million through the American Recovery & Reinvestment Act (ARRA), the project set out to combine the strong epidemiological research and comprehensive, consistent health records at Kaiser Permanente with UCSF’s strengths in genetics and telomere research, to create a national resource that would transform health science into the foreseeable future.

The overall project links a genetic analysis of 110,266 saliva samples collected at Kaiser Permanente of Northern California over the past five years to decades of Kaiser Permanente health records, as well as UCSF measurements of longevity markers and state environmental exposures. That health data includes thousands of pharmacy records and years of cholesterol and lipid tests, as well as mammograms, EKGs and MRI scans, all performed in the same laboratories with consistent techniques.

That is an invaluable resource, the researchers said, and already is starting to show results.

“We discovered 103 different genes underlying HDL
and LDL cholesterol and triglyceride levels,
with p values (statistical significance) that have
never been seen before, and there’s more to come.”

Neil Risch, PhD
director UCSF Institute for Human Genetics
joint leader with Cathy Schaefer, PhD
the Kaiser Permanente Division of Research

“What underlies these traits and diseases are many, many genes,” said Risch, a statistical geneticist who already has uncovered numerous genetic SNPS (single nucleotide polymorphisms) through this project that have never before been detected. “To see them all, you need very large samples. That’s what we have in this project.”

Its first results are both substantiating and refuting findings from smaller projects, while posing new questions for scientists to tackle in the years to come.

“We’re at the beginning of some really interesting
analyses of telomere length,” said Schaefer, an
epidemiologist who led the analyses of the telomere data,
after the telomeres were measured in the UCSF
laboratory of Nobel laureate Elizabeth Blackburn, PhD.

“We know that telomere length declines with age and
several studies have shown that telomere length is related
to a number of diseases,” Schaefer said. “The question
is whether the length is simply a marker of cumulative
experiences, or whether it plays a direct role in health.”

Some Surprising Findings on Telomeres

The initial findings, which stem from a one-year extension to begin analyses using the remainder of the team’s ARRA funding, were presented as talks and posters during the American Society of Human Genetics conference in San Francisco on Nov. 7-8.

Among the findings were a number of genes connected to diabetes, cancer and autoimmune diseases, among other health conditions.

There also was clear evidence that telomeres are longer
in African-Americans and in people with higher
educational status, while they are shorter for people in
low socioeconomic communities.

Telomeres also rise sharply in men who are over 75
years old and in women over 80, which the researchers
said probably means that these individuals – through
genetics or long-term lifestyle – were programmed
on a cellular basis to outlast their peers.

Smoking and alcohol consumption also were directly
linked to shorter telomeres, with a direct correlation
between the number of packs of cigarettes smoked
during a lifetime and shorter DNA nibs on an
individual’s chromosomes, which the researchers
said validated the link between what we know about
overall health conditions and our cellular health.

But they found no link between exercise and
telomere length, which has previously been reported.

The great surprise so far, Schaefer said, is in participants
with the highest Body Mass Index, who consistently
showed longer telomeres. That’s despite extensive
data showing that these individuals have more health
problems and worse health prognoses overall

The UCSF Institute for Human Genetics, through its Genomics Core Facility, also derived genetic information at 700,000 or more locations in the genome for each individual.

The resulting combination of health and genetic data, which includes over 70 billion genotypes and took two years to collect and quantify, is currently available as a resource through the Kaiser Permanente-UCSF team for external researchers studying the genetic or environmental basis of disease.

Later this fall, much of the data also will be incorporated into a national database known as dbGAP, run by the National Institutes of Health, which will be available to researchers worldwide.

Related Stories:

Personalized Medicine Highlighted at UCSF Genetics Symposium

UCSF & Kaiser Complete Massive Genotyping Project

UCSF Researchers Are Mapping DNA from 100,000 People for Unique Kaiser Database

Original article: http://www.ucsf.edu/news/2012/11/13166/massive-genomics-project-answers-questions-poses-new-ones-health-genetics-and